Oxabicycles synthesis

Ring opening of oxabicyclic compounds as a strategy in organic synthesis 97MI37. 

Stereocontrolled synthesis of oxabicyclic (3-lactam antibiotics via [2- -2] cycloaddition of isocyanates to sugar vinyl ethers 96CC2689. 

While transition metal-catalyzed hydroboration is a well-established reaction, the same cannot be said for the transition metal-catalyzed hydroalumination. The synthetic utility of this reaction is only just beginning to emerge. Lautens has led the way in the use of hydroaluminations as the key step in the total synthesis of complex natural products. The synthesis of the anti-depressant sertraline130 involved the formation of the tetrahydronaphthalene core, and this is best achieved using the nickel-catalyzed hydroalumination of oxabicyclic alkenes (Table 16). 

Lautens also used this nickel-catalyzed hydroalumination methodology in the total synthesis of ionomycin 145. The starting compound was a [3.2.1]oxabicyclic alkene 143.144 Their rigid bicyclic structures can be used to introduce functional groups in a highly stereoselective manner. The synthesis of the key intermediate 144 involves the slow addition of DIBAL to the oxabicyclic alkene and the Ni(COD)2/(6T)-BINAP in toluene to afford 144 in 95% yield and 93-95% ee. (Scheme 18). 

In conclusion, this is the most practical and least expensive method available for the synthesis of [3.2.1]oxabicyclic compounds. 

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

Chiu P, Lautens M (1997) Using Ring-Opening Reactions of Oxabicyclic Compounds as a Strategy in Organic Synthesis. 190 1 -85... 

Cyclizations arising by intramolecular radical addition have been widely employed in the synthesis of oxygen and sulfur heterocycles. The tetra-hydrofuran derivatives (494) have been prepared in this way via alkoxyl radicals, generated in turn by photolysis of the unsaturated nitrites (495).431 Bridged oxabicyclic compounds have been similarly prepared,432 and the photodecomposition of a nitrite has been employed in the synthesis of the... 

Preliminary results on the enantioselective formation of sulfur and nitrogen mediumsized heterocycles by base-induced ring opening of hetero-oxabicyclic [3.2.1] and [3.3.1] systems have been reported.91 The reaction involves a deprotonation-C—O bond elimination sequence. The kinetics and mechanism of gas-phase unimolecular elimination reactions of some substituted aminoazoles have been studied as an aid to heterocycle synthesis.92... 

An efficient strategy for the synthesis of /raor-fused oxabicyclic systems involving this annulation followed by a Ramberg-Backlund olefination (Equation 47) as the key step is used for the ring contraction of 116 to give the oxepane 117 in 41% yield, in which the intermediates formed on a-chlorination and sulfone formation steps were used without purification <1996TL2865>. 

M. Chmielewski, Z. Kaluza, and B. Furman, Stereocontrolled synthesis of 1-oxabicyclic /1-lactam antibiotics via [2 + 2]cycloaddition of isocyanates to sugar vinyl ethers, Chem. Commun. (Cambridge), (1996) 2689-2696. 

Using Ring-Opening Reactions of Oxabicyclic Compounds as a Strategy in Organic Synthesis... 

McDevitt, R E, Fraser-Reid, B, A divergent route for a total synthesis of cyclophellitol and epicyclophellitol from a [2.2.2]oxabicyclic glycoside prepared from D-glucal, J. Org. Chem., 59, 3250-3252, 1994. 

This reaction is not useful for synthesis of the [2.2.1] oxabicyclic system attempts to prepare this system by alternate approaches have been unsuccessful. Again, a more detailed report of this chemistry will be published elsewhere. 

This sequence was recently used in the synthesis of the alkaloid (+ )-aspidophytine (19). The key sequence of reactions was initiated by treatment of diazo ketoester 15 with Rh2(OAc)4 to generate a transient metallocarbene that reacted with the proximal imido carbonyl group to form dipole 16 (06OL3275). A subsequent 1,3-dipolar cycloaddition across the tethered indole n-bond gave cycloadduct 17 in 97% yield. Oxabicycle 17 was then converted into 18 by the action of BF3 OEt2 in 70% yield and this compound was eventually converted into ( )-aspidophytine (19). 

In this review, methods for the construction of oxabicyclic substrates of general structure 1, Fig. 1, are described as well as ring opening reactions which are applicable to the synthesis of natural products. 

The aim of this section is to give an overview of the general approaches that have been employed. A comprehensive review of all of the methods used to date for the synthesis of oxabicyclic compounds is beyond the scope of the review. Instead, a focus on the preparation of those oxabicyclic systems for which ring opening reactions have been developed is described. The more recent achievements in this area will be emphasized. 

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